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The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial.
Myette-Côté, É, Durrer, C, Neudorf, H, Bammert, TD, Botezelli, JD, Johnson, JD, DeSouza, CA, Little, JP
American journal of physiology. Regulatory, integrative and comparative physiology. 2018;315(6):R1210-R1219
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Inflammation is associated with the pathogenesis of insulin resistance, type 2 diabetes (T2D), and related complications. Lifestyle therapy is a frontline treatment for improving glucose control in people with T2D. The main aim of this study was to determine whether reducing hyperglycaemia with a low-carbohydrate high-fat (LC) diet could lower markers of innate immune cell activation and systemic inflammation in people with T2D. A secondary aim was to examine if the combination of an LCHF diet with strategically timed postmeal walking was superior to an LCHF diet alone. The study is a randomised cross over study which enrolled Individuals with physician-diagnosed T2D to complete three short-term controlled-intervention periods. Sixteen participants were enrolled (men = 8 and women = 8) who were aged between 48 and 72 years. Results indicate that while LC and LC together with exercise (LC+Ex) led to superior improvements in glucose control and fasting proinsulin (the pro-hormone precursor to insulin) levels as compared with low-fat low glycaemic index diet (GL), all three diets (GL, LC and LC+Ex), appeared to lower a particular marker of cellular inflammation over the short-term. Authors conclude that an LCHF diet with or without daily postmeal walks improved four-day glycaemic control and fasting proinsulin levels compared with a GL diet.
Abstract
Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (-5%, P < 0.05), whereas both LC+Ex (-16%, P < 0.001) and LC (-12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: -32%, LC: -45%, and LC+Ex: -44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (-76%, P = 0.035) and a tendency for a reduction in LC (-70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (-27%, P = 0.001) and LC+Ex (-35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.
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Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial.
Barrett, B, Hayney, MS, Muller, D, Rakel, D, Brown, R, Zgierska, AE, Barlow, S, Hayer, S, Barnet, JH, Torres, ER, et al
PloS one. 2018;13(6):e0197778
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Susceptibility to acute respiratory infection (ARI), including the common cold and flu, have been shown to be influenced by psychological, social and behavioural factors. Given these previous associations, the aim of this study was to determine the preventive effects of meditation and exercise on ARI illness. This randomised controlled trial allocated 390 participants to one of three parallel groups either receiving 8-week training in mindfulness-based stress reduction (MBSR), 8-week training in moderate intensity exercise or observational control. ARI symptoms were assessed daily and various psychosocial factors were assessed at baseline and 4 times after the intervention. Blood and nasal wash samples were assessed with each ARI episode as well as at baseline, 1-month and 4-month post-intervention. This study found significant reductions in ARI illness incidence, duration and severity for participants in the MBSR group compared with controls. While this was also true for the exercise group, results were not as significant suggesting a slight advantage of mindfulness over exercise. Based on these results, the authors conclude both mindfulness and exercise should be encouraged and further research be conducted to better understand the benefits of these activities in sick populations.
Abstract
BACKGROUND Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN Randomized controlled prevention trial with three parallel groups. SETTING Madison, Wisconsin, USA. PARTICIPANTS Community-recruited adults who did not regularly exercise or meditate. METHODS 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS This trial was likely underpowered. TRIAL REGISTRATION Clinicaltrials.gov NCT01654289.
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Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative.
Stout, AC, Barbe, MF, Eaton, CB, Amin, M, Al-Eid, F, Price, LL, Lu, B, Lo, GH, Zhang, M, Pang, J, et al
BMC musculoskeletal disorders. 2018;19(1):1
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Individuals with osteoarthritis (OA) typically present with greater systemic inflammation and impaired glucose homeostasis. Currently it is unclear whether these factors are associated with early-stage OA, namely bone marrow lesions and swelling. The purpose of this cross-sectional study was to investigate the role of inflammation and glucose homeostasis in early-stage OA. Using baseline data from the Osteoarthritis Initiative, 343 participants were enrolled and tested for markers of inflammation and impaired glucose homeostasis. Bone marrow lesions and swelling were also assessed through imaging results. Results indicate that among individuals without OA, those with greater systemic inflammation were more likely to have bone marrow lesions and knee swelling. According to these results, the authors conclude that systemic inflammation and glucose homeostasis are related to structural features of osteoarthritis. Future studies should explore whether these factors are predictive of OA in order to identify therapeutic targets to prevent or delay the onset of knee OA.
Abstract
BACKGROUND Greater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features. We examined if serum concentrations of glucose homeostasis (glucose, glycated serum protein [GSP]) or inflammation (C-reactive protein [CRP]) were associated with prevalent knee bone marrow lesions (BMLs) or effusion among adults without knee OA. METHODS We conducted a cross-sectional study using baseline data from the Osteoarthritis Initiative. We selected participants who had no radiographic knee OA but were at high risk for knee OA. Blinded staff conducted assays for CRP, GSP, and glucose. Readers segmented BML volume and effusion using semi-automated programs. Our outcomes were prevalent BML (knee with a BML volume > 1 cm3) and effusion (knee with an effusion volume > 7.5 cm3). We used logistic regression models with CRP, GSP, or glucose concentrations as the predictors. We adjusted for age, sex, body mass index (BMI), and Physical Activity Scale for the Elderly (PASE) scores. RESULTS We included 343 participants: mean age = 59 ± 9 years, BMI = 27.9 ± 4.5 kg/m2, PASE score = 171 ± 82, and 64% female. Only CRP was associated with BML prevalence (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09 to 1.87). For effusion, we found an interaction between BMI and CRP: only among adults with a BMI <25 kg/m2 was there a significant trend towards a positive association between CRP and effusion (OR = 1.40, 95% CI = 1.00 to 1.97). We detected a U-shaped relationship between GSP and effusion prevalence. Fasting glucose levels were not significantly associated with the presence of baseline effusion or BML. CONCLUSIONS Among individuals without knee OA, CRP may be related to the presence of BMLs and effusion among normal weight individuals. Abnormal GSP may be associated with effusion. Future studies should explore whether inflammation and glucose homeostasis are predictive of symptomatic knee OA.
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Changes in Visceral Adiposity, Subcutaneous Adiposity, and Sex Hormones in the Diabetes Prevention Program.
Kim, C, Dabelea, D, Kalyani, RR, Christophi, CA, Bray, GA, Pi-Sunyer, X, Darwin, CH, Yalamanchi, S, Barrett-Connor, E, Golden, SH, et al
The Journal of clinical endocrinology and metabolism. 2017;102(9):3381-3389
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It is not currently known to what extent changes in different types of fat stores (visceral fat that surrounds organs and subcutaneous fat that sits under the surface of the skin) relate to changes in sex hormones. This study was a secondary analysis of a randomised controlled trial including 555 individuals. It examined whether changes to visceral and subcutaneous fat were associated with changes in sex hormones (DHEA, testosterone, oestrogen and sex hormone binding globulin - SHBG) among overweight individuals with glucose intolerance under the care of a diabetes program. Participants were randomly assigned to an intensive lifestyle modification programme (goals for weight reduction and 150 mins exercise weekly), medication (metformin) or placebo for 12 months. The authors found that among men, reductions in both types of fat were associated with significant increases in total testosterone and SHBG. Among women, reductions in both types of fat were associated with increases in SHBG and associations with estrone differed by menopausal status. No associations were found between changes in fat stores and estradiol or DHEA. The authors conclude that weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat. -
Abstract
Context: The degree to which changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) relate to corresponding changes in plasma sex steroids is not known. Objective: We examined whether changes in VAT and SAT areas assessed by computed tomography were associated with changes in sex hormones [dehydroepiandrosterone sulfate (DHEAS), testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG)] among Diabetes Prevention Program participants. Design: Secondary analysis of a randomized trial. Participants: Overweight and glucose-intolerant men (n = 246) and women (n = 309). Interventions: Intensive lifestyle change with goals of weight reduction and 150 min/wk of moderate intensity exercise or metformin administered 850 mg twice a day or placebo. Main Outcome Measures: Associations between changes in VAT, SAT, and sex hormone changes over 1 year. Results: Among men, reductions in VAT and SAT were both independently associated with significant increases in total testosterone and SHBG in fully adjusted models. Among women, reductions in VAT and SAT were both independently associated with increases in SHBG and associations with estrone differed by menopausal status. Associations were similar by race/ethnicity and by randomization arm. No significant associations were observed between change in fat depot with change in estradiol or DHEAS. Conclusions: Among overweight adults with impaired glucose intolerance, reductions in either VAT and SAT were associated with increased total testosterone in men and higher SHBG in men and women. Weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat.
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Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Demark-Wahnefried, W, Nix, JW, Hunter, GR, Rais-Bahrami, S, Desmond, RA, Chacko, B, Morrow, CD, Azrad, M, Frugé, AD, Tsuruta, Y, et al
BMC cancer. 2016;16:61
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There is a strong body of evidence associating obesity and increased risk for more aggressive and progressive cancer. This paper aims to assess the feasibility of a presurgical diet and exercise weight loss intervention in men with newly-diagnosed prostate cancer who elected for prostatectomy. It also aims to explore the intervention’s effects on tumour proliferation rates and other biomarkers. The 3-weeks randomised controlled study included 40 overweight or obese men newly-diagnosed with prostate cancer. Participants in experimental arm were assigned to a healthy energy-restricted diet versus wait-list control arm. All feasibility endpoints were achieved with accrual completed within 2 years, retention of 85%, adherence of 95% and no adverse events. Biologic outcomes were not included in this paper, as biological testing was still ongoing. Authors concluded that this study’s methods and data on feasibility could provide useful framework for the design of future trials. They also highlighted the importance of presurgical trials as a feasible and safe means to assess the impacts of diet and exercise on tumour tissue.
Abstract
BACKGROUND Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION NCT01886677.
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Reversal of cognitive decline in Alzheimer's disease.
Bredesen, DE, Amos, EC, Canick, J, Ackerley, M, Raji, C, Fiala, M, Ahdidan, J
Aging. 2016;8(6):1250-8
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Alzheimer’s disease is the third leading cause of death and is one of the most significant global healthcare problems of modern times. It leads initially to cognitive decline – inability to recall words and faces, do mental calculations, navigate on familiar routes – and eventually to complete loss of memory and ability to perform routine daily tasks. Conventional therapy focuses on single drug therapies and success with these has been limited. This case study report details the results of 10 patients experiencing differing degrees of cognitive decline and early Alzheimer’s disease. Each patient followed a personalised, multiple therapy programme for 5 months to 2 years, based on their genetics, markers for blood glucose management, lipid profile, homocysteine, Vitamin D and inflammation, amongst others. Each case reports a quantified improvement in brain function, as well as subjective improvements reported by the carers and patients. The authors call for funding for a randomised controlled trial and for early detection and treatment using a multi-faceted protocol. Nutrition Practitioners working with cognitive decline can use the case study reports to inform their testing choices and personalised nutrition and lifestyle protocols.
Abstract
Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype.
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Metabolic profiling distinguishes three subtypes of Alzheimer's disease.
Bredesen, DE
Aging. 2015;7(8):595-600
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The causes of Alzheimer’s Disease (AD) remain incompletely defined and there are currently no truly effective drug therapies available. However, there is growing evidence that disordered blood glucose management and hormonal changes and deficiencies, amongst other things, are implicated in symptom onset. Optimising these various metabolic processes, therefore, may be used as a comprehensive way to avoid cognitive decline or achieve cognitive improvements in symptomatic individuals. This report provides the metabolic results of 3 case studies and suggests 3 different types of AD classification, depending on the individual metabolic profile. Further studies are required to elaborate on the metabolic profiles suggested in this report, however Nutrition Practitioners working with cognitive decline, can use this report as a basis for individualised nutrition protocols to optimise metabolic processes in clients with cognitive decline.
Abstract
The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization.
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Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults.
Napoli, N, Shah, K, Waters, DL, Sinacore, DR, Qualls, C, Villareal, DT
The American journal of clinical nutrition. 2014;100(1):189-98
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Obese adults may be at increased risk of dementia. Lifestyle interventions and weight loss are recommended for obese individuals, however, this may not be applicable to older obese individuals as extra weight could be protective against health risks in the older generation. This randomised controlled trail aimed to evaluate the combined and independent effect of weight loss and exercise on cognition & mood in 107 obese older adults over a one year period. The study found that diet and exercise both independently had a statistically significant impact on mood and quality of life. Exercise had the most significant impact, with the combination of diet and exercise being equal to the impact of exercise alone.
Abstract
BACKGROUND Obesity impairs cognition and health-related quality of life (HRQOL) in older adults; however, the appropriate treatment of obese older adults remains controversial. OBJECTIVE The objective was to determine the independent and combined effects of weight loss and exercise on cognition, mood, and HRQOL in obese older adults. DESIGN One hundred seven frail, obese older adults were randomly assigned to a control, weight-management (diet), exercise, or weight-management-plus-exercise (diet-exercise) group for 1 y. In this secondary analysis, main outcomes were Modified Mini-Mental State Examination (3MS) and total Impact of Weight on Quality of Life-Lite (IWQOL) scores. Other outcomes included Word Fluency Test, Trail Making Test Parts A and B, and Geriatric Depression Scale (GDS) scores. RESULTS Scores on the 3MS improved more in the diet (mean ± SE: 1.7 ± 0.4), exercise (2.8 ± 0.4), and diet-exercise (2.9 ± 0.4) groups than in the control group (0.1 ± 0.4) (between-group P = 0.0001-0.04); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. Scores on the Word Fluency Test improved more in the exercise (4.1 ± 0.8) and diet-exercise (4.2 ± 0.7) groups than in the control group (-0.8 ± 0.8; both P = 0.001). For the Trail Making Test Part A, scores in the diet-exercise group (-11.8 ± 1.9) improved more than in the control group (-0.8 ± 1.9) (P = 0.001); a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet (7.6 ± 1.6), exercise (10.1 ± 1.6), and diet-exercise (14.0 ± 1.4) groups than in the control group (0.3 ± 1.6) (P = 0.0001-0.03); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. In the diet-exercise group, peak oxygen consumption and strength changes were independent predictors of 3MS changes; weight and strength changes were independent predictors of IWQOL changes. GDS scores did not change. CONCLUSIONS Weight loss and exercise each improve cognition and HRQOL, but their combination may provide benefits similar to exercise alone. These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults. This trial was registered atclinicaltrials.govas NCT00146107.
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Glycemic index, glycemic load, and risk of type 2 diabetes: results from 3 large US cohorts and an updated meta-analysis.
Bhupathiraju, SN, Tobias, DK, Malik, VS, Pan, A, Hruby, A, Manson, JE, Willett, WC, Hu, FB
The American journal of clinical nutrition. 2014;100(1):218-32
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Carbohydrates are the principle dietary components that effect blood glucose concentrations. The association between Type 2 diabetes (T2D) and diets with different levels of sugars and carbohydrates has been controversial in the prevention of T2D. Foods can be measured for their impact on blood glucose concentration using the Glycaemic Index (GI) and the Glycaemic Load (GL). The objective of this meta-analysis was to update previous studies and evaluate the association between the GI and GL of dietary intake and the risk of T2D. The authors found a significant association between the GI and GL of food intake and T2D risk and conclude that high GI and GL foods increase the risk of T2D. However, GI is more strongly associated to T2D than GL.
Abstract
BACKGROUND Epidemiologic evidence for the relation between carbohydrate quality and risk of type 2 diabetes (T2D) has been mixed. OBJECTIVE We prospectively examined the association of dietary glycemic index (GI) and glycemic load (GL) with T2D risk. DESIGN We prospectively followed 74,248 women from the Nurses' Health Study (1984-2008), 90,411 women from the Nurses' Health Study II (1991-2009), and 40,498 men from the Health Professionals Follow-Up Study (1986-2008) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by using a validated questionnaire and updated every 4 y. We also conducted an updated meta-analysis, including results from our 3 cohorts and other studies. RESULTS During 3,800,618 person-years of follow-up, we documented 15,027 cases of incident T2D. In pooled multivariable analyses, those in the highest quintile of energy-adjusted GI had a 33% higher risk (95% CI: 26%, 41%) of T2D than those in the lowest quintile. Participants in the highest quintile of energy-adjusted GL had a 10% higher risk (95% CI: 2%, 18%) of T2D. Participants who consumed a combination diet that was high in GI or GL and low in cereal fiber had an ~50% higher risk of T2D. In the updated meta-analysis, the summary RRs (95% CIs) comparing the highest with the lowest categories of GI and GL were 1.19 (1.14, 1.24) and 1.13 (1.08, 1.17), respectively. CONCLUSION The updated analyses from our 3 cohorts and meta-analyses provide further evidence that higher dietary GI and GL are associated with increased risk of T2D.
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Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes.
Wing, RR, Bolin, P, Brancati, FL, Bray, GA, Clark, JM, Coday, M, Crow, RS, Curtis, JM, Egan, CM, Espeland, MA, et al
The New England journal of medicine. 2013;369(2):145-54
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Weight loss is recommended for overweight or obese patients with type 2 diabetes as it increases glycaemic control, reduces risk factors of cardiovascular disease and improves overall quality of life. These benefits, however, are based on short-term studies and the long-term effects of weight loss in this population have not been examined. The aim of this randomised trial was to elucidate whether an intensive lifestyle intervention of weight loss and increased physical activity would decrease cardiovascular morbidity and mortality in overweight or obese adults with type 2 diabetes. Participants were either assigned to an intervention group receiving diet and exercise counselling, or a control group receiving diabetes support and education. A total of 5145 patients were enrolled in the study and the median follow-up was nearly 10 years. The findings of this study showed that an intensive lifestyle intervention did not reduce the risk of cardiovascular morbidity and mortality, as compared with a control programme of diabetes support and education, among overweight and obese patients. While this primary outcome was not reduced, participants in the intervention group experienced various clinically beneficial outcomes throughout the follow-up period.
Abstract
BACKGROUND Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).